Montelukast Reversed Immunotherapy Resistance in Mice by Targeting CysLTR1, Extending Survival Across 3 Cancers
Updated
Updated · Livescience.com · May 20
Montelukast Reversed Immunotherapy Resistance in Mice by Targeting CysLTR1, Extending Survival Across 3 Cancers
5 articles · Updated · Livescience.com · May 20
Nature Cancer published preclinical data showing montelukast or genetic CysLTR1 blockade slowed tumor growth, prolonged survival and made previously resistant tumors respond to checkpoint inhibitors in mouse breast, colon and melanoma-like cancers.
Researchers said tumors exploit CysLTR1 to reprogram neutrophils into immune-suppressing cells that help cancers invade tissue and evade attacks from other immune cells, helping drive resistance to immunotherapy.
Human blood-cell experiments and cancer-dataset analyses pointed the same way: blocking CysLTR1 reduced neutrophils' suppressive behavior, while higher receptor levels in tumors tracked with worse outcomes and weaker checkpoint-blockade responses.
Montelukast has been FDA-approved since 1998 for asthma and hay fever, which could ease trial design, but researchers and outside experts said cancer use remains early and needs dosing, safety and patient-selection studies.
The work also raises CysLTR1 as a possible biomarker for predicting immunotherapy resistance, though montelukast's 2020 boxed warning over neuropsychiatric side effects could complicate repurposing.
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